Exploring the role of peripheral nerves in trauma-induced heterotopic ossification.

Recent studies have linked pain and the resultant nociception-induced neural inflammation (NINI) to trauma-induced heterotopic ossification (THO). It is postulated that nociception at the injury site stimulates the transient receptor potential vanilloid-1 (the transient receptor potential cation channel subfamily V member 1) receptors on sensory nerves within the injured tissues resulting in the expression of neuroinflammatory peptides, substance P (SP), and calcitonin gene-related peptide (CGRP). Additionally, BMP-2 released from fractured bones and soft tissue injury also selectively activates TRVP1 receptors, resulting in the release of SP and CGRP and causing neuroinflammation and degranulation of mast cells causing the breakdown the blood-nerve barrier (BNB), leading to release of neural crest derived progenitor cells (NCDPCs) into the injured tissue.

Interindividual Variability in Postprandial Plasma Fructose Patterns in Adults.

High fructose consumption is associated with an increased risk of cardiometabolic disease, and fructose feeding dose-dependently induces markers reflective of poor metabolic health. However, unlike glucose, surprisingly little is known about person-to-person differences in postprandial plasma fructose patterns. Herein, we performed post hoc analyses of two published studies to address this question.

The mouse metabolic phenotyping center (MMPC) live consortium: an NIH resource for in vivo characterization of mouse models of diabetes and obesity.

The Mouse Metabolic Phenotyping Center (MMPC)Live Program was established in 2023 by the National Institute for Diabetes, Digestive and Kidney Diseases (NIDDK) at the National Institutes of Health (NIH) to advance biomedical research by providing the scientific community with standardized, high quality phenotyping services for mouse models of diabetes and obesity. Emerging as the next iteration of the MMPC Program which served the biomedical research community for 20 years (2001-2021), MMPCLive is designed as an outwardly-facing consortium of service cores that collaborate to provide reduced-cost consultation and metabolic, physiologic, and behavioral phenotyping tests on live mice for U.S.

Novel odd-chain cyclopropane fatty acids: detection in a mammalian lipidome and uptake by hepatosplanchnic tissues.

Microbe-produced molecules (xenometabolites) found in foods or produced by gut microbiota are increasingly implicated in microbe-microbe and microbe-host communication. Xenolipids, in particular, are a class of metabolites for which the full catalog remains to be elaborated in mammalian systems. We and others have observed that cis-3,4-methylene-heptanoylcarnitine is a lipid derivative that is one of the most abundant medium-chain acylcarnitines in human blood, hypothesized to be a product of incomplete β-oxidation of one or more "odd-chain" long-chain cyclopropane fatty acids (CpFAs).

A versatile delivery vehicle for cellular oxygen and fuels or metabolic sensor? A review and perspective on the functions of myoglobin.

A canonical view of the primary physiological function of myoglobin (Mb) is that it is an oxygen (O) storage protein supporting mitochondrial oxidative phosphorylation, especially as the tissue O partial pressure (Po) drops and Mb off-loads O. Besides O storage/transport, recent findings support functions for Mb in lipid trafficking and sequestration, interacting with cellular glycolytic metabolites such as lactate (LAC) and pyruvate (PYR), and "ectopic" expression in some types of cancer cells and in brown adipose tissue (BAT). Data from Mb knockout (Mb) mice and biochemical models suggest additional metabolic roles for Mb, especially regulation of nitric oxide (NO) pools, modulation of BAT bioenergetics, thermogenesis, and lipid storage phenotypes.

Computational Analysis Reveals Unique Binding Patterns of Oxygenated and Deoxygenated Myoglobin to the Outer Mitochondrial Membrane.

Myoglobin (Mb) interaction with the outer mitochondrial membrane (OMM) promotes oxygen (O) release. However, comprehensive molecular details on specific contact regions of the OMM with oxygenated (oxy-) and deoxygenated (deoxy-)Mb are missing. We used molecular dynamics (MD) simulations to explore the interaction of oxy- and deoxy-Mb with the membrane lipids of the OMM in two lipid compositions: (a) a typical whole membrane on average, and (b) specifically the cardiolipin-enriched cristae region (contact site).

Elevated LDL-C, high blood pressure, and low peak O associate with platelet mitochondria function in children-The Arkansas Active Kids Study.

To evaluate the association of platelet (PL) mitochondria respiration with markers of cardiovascular health in children ages 7-10 years. PL mitochondrial respiration (n = 91) was assessed by high resolution respirometry (HRR): Routine (R) respiration, complex (C) I linked respiration (CI), and maximal uncoupled electron transport capacity of CII (CII) were measured. The respiratory control ratio (RCR) was calculated as the ratio of maximal oxidative phosphorylation capacity of CI and CI leak respiration (P/L).

Exercise training modifies xenometabolites in gut and circulation of lean and obese adults.

Regular, moderate exercise modifies the gut microbiome and contributes to human metabolic and immune health. The microbiome may exert influence on host physiology through the microbial production and modification of metabolites (xenometabolites); however, this has not been extensively explored. We hypothesized that 6 weeks of supervised, aerobic exercise 3×/week (60%-75% heart rate reserve [HRR], 30-60 min) in previously sedentary, lean (n = 14) and obese (n = 10) adults would modify both the fecal and serum xenometabolome.

Myoglobin-Pyruvate Interactions: Binding Thermodynamics, Structure-Function Relationships, and Impact on Oxygen Release Kinetics.

Myoglobin (Mb), besides its roles as an oxygen (O) carrier/storage protein and nitric oxide NO scavenger/producer, may participate in lipid trafficking and metabolite binding. Our recent findings have shown that O is released from oxy-Mb upon interaction with lactate (LAC, anerobic glycolysis end-product). Since pyruvate (PYR) is structurally similar and metabolically related to LAC, we investigated the effects of PYR (aerobic glycolysis end-product) on Mb using isothermal titration calorimetry, circular dichroism, and O-kinetic studies to evaluate PYR affinity toward Mb and to compare the effects of PYR and LAC on O release kinetics of oxy-Mb.

C-section increases cecal abundance of the archetypal bile acid and glucocorticoid modifying Lachnoclostridium [clostridium] scindens in mice.

In humans and animal models, Cesarean section (C-section) has been associated with alterations in the taxonomic structure of the gut microbiome. These changes in microbiota populations are hypothesized to impact immune, metabolic, and behavioral/neurologic systems and others. It is not clear if birth mode inherently changes the microbiome, or if C-section effects are context-specific and involve interactions with environmental and other factors.

Assessing Insulin Sensitivity and Postprandial Triglyceridemic Response Phenotypes With a Mixed Macronutrient Tolerance Test.

Unlabelled: The use of meal challenge tests to assess postprandial responses in carbohydrate and fat metabolism is well established in clinical nutrition research. However, challenge meal compositions and protocols remain a variable. Here, we validated a mixed macronutrient tolerance test (MMTT), containing 56-g palm oil, 59-g sucrose, and 26-g egg white protein for the parallel determination of insulin sensitivity and postprandial triglyceridemia in clinically healthy subjects.

Myoglobin Interaction with Lactate Rapidly Releases Oxygen: Studies on Binding Thermodynamics, Spectroscopy, and Oxygen Kinetics.

Myoglobin (Mb)-mediated oxygen (O) delivery and dissolved O in the cytosol are two major sources that support oxidative phosphorylation. During intense exercise, lactate (LAC) production is elevated in skeletal muscles as a consequence of insufficient intracellular O supply. The latter results in diminished mitochondrial oxidative metabolism and an increased reliance on nonoxidative pathways to generate ATP.

Effects of a diet based on the Dietary Guidelines on vascular health and TMAO in women with cardiometabolic risk factors.

Background And Aims: Recent evidence links trimethylamine oxide (TMAO) to endothelial dysfunction, an early indicator of cardiovascular disease. We aimed to determine whether short-term consumption of a diet patterned after the 2010 Dietary Guidelines for Americans (DGA) would affect endothelial function, plasma TMAO concentrations, and cardiovascular disease risk, differently than a typical American Diet (TAD).

Methods And Results: An 8-wk controlled feeding trial was conducted in overweight/obese women pre-screened for insulin resistance and/or dyslipidemia.

Progression of diabetes is associated with changes in the ileal transcriptome and ileal-colon morphology in the UC Davis Type 2 Diabetes Mellitus rat.

Deterioration in glucose homeostasis has been associated with intestinal dysbiosis, but it is not known how metabolic dysregulation alters the gastrointestinal environment. We investigated how the progression of diabetes alters ileal and colonic epithelial mucosal structure, microbial abundance, and transcript expression in the University of California Davis Type 2 Diabetes Mellitus (UCD-T2DM) rat model. Male UCD-T2DM rats (age ~170 days) were included if <1-month (n = 6, D1M) or 3-month (n = 6, D3M) post-onset of diabetes.

The Effects of Blueberry Phytochemicals on Cell Models of Inflammation and Oxidative Stress.

Blueberries have been extensively studied for the health benefits associated with their high phenolic content. The positive impact of blueberry consumption on human health is associated in part with modulation of proinflammatory molecular pathways and oxidative stress. Here, we review in vitro studies examining the anti-inflammatory and antioxidant effects of blueberry phytochemicals, discuss the results in terms of relevance to disease and health, and consider how different blueberry components modulate cellular mechanisms.

Sex differences in skeletal muscle revealed through fiber type, capillarity, and transcriptomics profiling in mice.

Skeletal muscle anatomy and physiology are sexually dimorphic but molecular underpinnings and muscle-specificity are not well-established. Variances in metabolic health, fitness level, sedentary behavior, genetics, and age make it difficult to discern inherent sex effects in humans. Therefore, mice under well-controlled conditions were used to determine female and male (n = 19/sex) skeletal muscle fiber type/size and capillarity in superficial and deep gastrocnemius (GA-s, GA-d), soleus (SOL), extensor digitorum longus (EDL), and plantaris (PLT), and transcriptome patterns were also determined (GA, SOL).

Cardiorespiratory Fitness Associates with Blood Pressure and Metabolic Health of Children-The Arkansas Active Kids Study.

Introduction: High blood pressure (HBP) in children causes preclinical damage to the heart and accelerates atherosclerosis. Current pharmacological treatments have limited ability to prevent end-organ damage, particularly that of the kidneys. A contrasting element between adult versus pediatric HPB treatment is the emphasis in adults on exercise regimens that target increments in cardiorespiratory fitness (CRF; peak oxygen consumption [V˙O2peak]).

On the potential role of globins in brown adipose tissue: a novel conceptual model and studies in myoglobin knockout mice.

Myoglobin (Mb) regulates O bioavailability in muscle and heart as the partial pressure of O (Po) drops with increased tissue workload. Globin proteins also modulate cellular NO pools, "scavenging" NO at higher Po and converting NO to NO as Po falls. Myoglobin binding of fatty acids may also signal a role in fat metabolism.

Metabolic physiology and skeletal muscle phenotypes in male and female myoglobin knockout mice.

Myoglobin (Mb) is a regulator of O bioavailability in type I muscle and heart, at least when tissue O levels drop. Mb also plays a role in regulating cellular nitric oxide (NO) pools. Robust binding of long-chain fatty acids and long-chain acylcarnitines to Mb, and enhanced glucose metabolism in hearts of Mb knockout (KO) mice, suggest additional roles in muscle intermediary metabolism and fuel selection.

Diet affects glycosylation of serum proteins in women at risk for cardiometabolic disease.

Background: Glycoproteomics deals with glycoproteins that are formed by post-translational modification when sugars (like fucose and sialic acid) are attached to protein. Glycosylation of proteins influences function, but whether glycosylation is altered by diet is unknown.

Objective: To evaluate the effect of consuming a diet based on the Dietary Guidelines for Americans on circulating glycoproteins that have previously been associated with cardiometabolic diseases.

Exercise training and diet-induced weight loss increase markers of hepatic bile acid (BA) synthesis and reduce serum total BA concentrations in obese women.

Regular exercise has profound metabolic influence on the liver, but effects on bile acid (BA) metabolism are less well known. BAs are synthesized exclusively in the liver from cholesterol via the rate-limiting enzyme cholesterol 7 alpha-hydroxylase (CYP7A1). BAs contribute to the solubilization and absorption of lipids and serve as important signaling molecules, capable of systemic endocrine function.

Human Milk-Fed Piglets Have a Distinct Small Intestine and Circulatory Metabolome Profile Relative to That of Milk Formula-Fed Piglets.

The impact of human milk (HM) feeding compared with cow's milk formula (MF) feeding on small intestinal and circulatory metabolome patterns has not been fully investigated. Therefore, 2-day-old male piglets were fed HM or MF ( = 26/group) from postnatal day 2 (PND 2) through 21 and were weaned to a solid diet until PND 51. The small intestine (gastrointestinal [GI]) contents, serum, and urine were collected from subsets of piglets at PND 21 and PND 51.

Neonatal Diet Impacts the Large Intestine Luminal Metabolome at Weaning and Post-Weaning in Piglets Fed Formula or Human Milk.

The impact of human milk (HM) or dairy milk-based formula (MF) on the large intestine's metabolome was not investigated. Two-day old male piglets were randomly assigned to HM or MF diet (n = 26/group), from postnatal day (PND) 2 through 21 and weaned to a solid diet until PND 51. Piglets were euthanized at PND 21 and PND 51, luminal contents of the cecum, proximal (PC) and distal colons (DC), and rectum were collected and subjected to metabolomics analysis.